Abstract
Aims: Tumour necrosis factor-alpha is a proinflammatory cytokine that has been implicated in the inflammatory response to bacterial infection and wear debris particles around loosened total hip replacements (THR). Individual TNF responses to such stimuli may be dictated by genetic variation and we have studied the effect of single nucleotide polymorphisms (SNPs) within the TNF gene.
Methods: We performed a case control study of 9 SNPs (−1031, −863, −857, −376, −308, −238, +489, +851 and +1304) for possible association with deep sepsis or aseptic loosening. All patients included in the study were Caucasian and had had a cemented Charnley THR. Cases consisted of 44 patients with early aseptic loosening and 30 patients with microbiological evidence at surgery of deep infection. Controls consisted of 85 THRs that were clinically asymptomatic for over 10 years and demonstrated no radiographic features of aseptic loosening. DNA was extracted from venous blood and genotyped by Snapshot assay.
Results: Genotype and allele frequencies for all SNPs were in Hardy-Weinberg equilibrium between THR controls and a random sample of UK Caucasians. A significant association was found for the -863 SNP and aseptic loosening (p< 0.05; OR=2.36; 95% CI: 0.976 – 5.71). A trend towards association was found between the -863A SNP and deep infection (p=0.80; OR=2.42; CI: 0.800 – 7.34).
Conclusions: Genetic polymorphism of TNF-alpha may play a significant role in THR aseptic loosening and possibly in deep infection. SNP markers may serve as predictors of implant survival and response to therapy such as anti-TNF treatment.
Correspondence should be addressed to Carlos Widgerowitz, Honorary Secretary BORS, Division of Surgery and Oncology, Section of Orthopaedic and Trauma Surgery, Ninewells Hospital and Medical School, Tort Centre, Dundee DD1 9SY, Scotland.
